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Background: As a routine procedure in assisted reproductive technology (ART), it is crucial to assess the safety of frozen and thawed embryo transfer (FET). We aimed to investigate the metabolic profile of children conceived through FET in their early childhood. Method: A total of 147 children between the age of 1.5 and 4 years old, conceived through FET or naturally conceived (NC), were recruited. A total of 89 children, 65 in the FET group and 24 in the NC group (matched with the FET group based on children’s BMI) were included in the final statistical analysis of biochemical markers and metabolomics. Results: Children conceived through FET had a lower level of fasting insulin level and HORM-IR and a higher level of fasting glucose and APOE as compared to children naturally conceived. Metabolomics showed that there were 16 small differential metabolites, mainly including amino acids, carnitines, organic acids, butyric, and secondary bile acid between two groups, which enriched in Nitrogen metabolism, Butanoate metabolism, Phenylalanine metabolism, and D-Arginine and D-ornithine metabolism pathways. Conclusion: Although the FET group had a significantly higher level of APOE and fasting glucose, it cannot yet be considered that children in the FET group had an obvious disorder of glucose and lipid metabolism. However, the potentially more active intestinal flora and lower carnitine levels of children in the FET group suggested by metabolomics are worth further exploration.

Hyaluronan is a structural component of the expanded cumulus matrix, and hyaluronan synthase 2 is the major enzyme for the synthesis of hyaluronan in humans. Versican cross-links the hyaluronan-rich matrix to cumulus cells and is critical for successful ovulation. Activin A is a critical intrafollicular regulator of ovarian function. Although activin A has been shown to promote cumulus matrix expansion in mice, the functional role of activin A in the regulation of cumulus expansion in the human ovary remains to be elucidated. Using primary and immortalized human granulosa-lutein cells as study models, we provide the first data showing that activin A increased the production of hyaluronan by upregulating the expression of hyaluronan synthase 2 in these cells. Additionally, activin A also promoted the expression of the hyaluronan-binding protein versican. Moreover, using inhibitor- and small interfering RNA-mediated inhibition approaches, we found that these stimulatory effects of activin A are most likely mediated through the type I receptor activin receptor-like kinase (ALK4)-mediated Sma- and Mad-related protein (SMAD2)/SMAD3-SMAD4 signaling pathway. Notably, the chromatin immunoprecipitation analyses demonstrated that SMAD4 could bind to human hyaluronan synthase 2 and VERSICAN promoters. The results obtained from this in vitro study suggest that locally produced activin A plays a functional role in the regulation of hyaluronan production and stabilization in human granulosa-lutein cells.

In recent years, the developmental origins of diseases have been increasingly recognized and accepted. As such, it has been suggested that most adulthood chronic diseases such as diabetes, obesity, cardiovascular disease, and even tumors may develop at a very early stage. In addition to intrauterine environmental exposure, germ cells carry an important inheritance role as the primary link between the two generations. Adverse external influences during differentiation and development can cause damage to germ cells, which may then increase the risk of chronic disease development later in life. Here, we further elucidate and clarify the concept of gamete and embryo origins of adult diseases by focusing on the environmental insults on germ cells, from differentiation to maturation and fertilization.

We tested the hypothesis of whether maternal residential proximity to municipal solid waste incinerator (MSWI) sites could significantly affect birth outcomes. This retrospective birth cohort study conducted at the International Peace Maternity and Infant Hospital, Shanghai, China, included 59,606 mothers with singleton live births during 2014-2018. Multivariate generalized linear models were used to examine associations between residential proximity to MSWI sites and birth outcomes. Small for gestational age (SGA) was significantly more common among children with maternal residential proximity to MSWI sites (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.07-1.34). Maternal prepregnancy body mass index (BMI) influenced this association. Infants of underweight mothers (prepregnancy BMI

Background There has been increasing interest in the relationship between body mass index(BMI) and pregnancy outcomes, especially in women undergoing frozen embryo transfer(FET). Several observational studies have been published, but so far with conflicting results. Methods A systematic review and meta-analysis was conducted according to PRISMA guidelines. Pubmed, Embase, Cochrane Library, Clinicaltrails.gov and Web of Science databases were searched based on established search strategy from inception through January 2021. Results Twelve studies were eligible. In women following FET, high BMI (BMI ≥ 23 kg/m2) was associated with an impaired live birth rate (LBR, OR: 0.89, 95% CI: 0.82–0.96, P = 0.002), but wasn’t associated with the implantation rate or the clinical pregnancy rate. Subgroup analysis revealed higher LBR for women didn’t complicated by polycystic ovary syndrome (PCOS, OR: 0.96, 95% CI: 0.85–1.08, P = 0.46) and women with blastocyst transferred (OR: 0.89, 95% CI: 0.68–1.16, P = 0.40). LBR did not differ between the low BMI group (BMI 2) and the normal weight group. Conclusions Our study showed that high BMI in women is negatively associated with LBR in FET cycles, whereas low BMI isn’t. The results of subgroup analysis implied a need for women with a high BMI to get individualized weight management and treatment. Further evidence is still required to optimize preconception health and develop Nutritional and exercise guidelines.

The long noncoding RNA (lncRNA) THOR is highly conserved and expressed in various human cancer tissues, although its potential role and underlying mechanism in endometrial cancer (EC) remain unknown. This study aims to explore THOR's biological function and molecular mechanism in EC progression. THOR expression in EC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR) and in situ hybridization (ISH). THOR expression based on The Cancer Genome Atlas (TCGA) and clinical sample analyses was significantly higher in EC tissues than normal tissues, and higher THOR levels were closely associated with poor overall survival in EC. Additionally, a positive correlation between ISH-detected THOR expression and pathological grade was observed. CCK-8, colony formation, and transwell migration and invasion assays revealed that THOR significantly enhances the proliferation, migration, and invasion abilities of EC cells. Moreover, IGF2BP1 protein expression and ERK and AKT protein phosphorylation levels in EC cells increased significantly with THOR overexpression in EC cells. In conclusion, our findings suggest that THOR promotes EC cell growth and invasion, and IGF2BP1-mediated AKT and ERK signaling pathways activation might be involved. Clinically, THOR is significantly expressed in EC, and high THOR expression correlates with poor prognosis, making it a potential prognostic marker for EC.

Background COVID-19 pandemic has had direct and indirect impacts on health-care system and maternal and neonatal health, but no multicenter evidence from China of this effects has been undertaken. The purpose of this study was to investigate the impacts of COVID-19 lockdown on maternal and fetal outcomes in China. Methods This retrospective cohort study included 3540 women in their late pregnancy without COVID-19 who received perinatal healthcare in three hospitals in Wuhan, Shanghai and Haikou during COVID-19 lockdown period in 2020 or the non-lockdown period in 2019. Propensity-score matching was used to compare preterm birth (

Recurrent pregnancy loss (RPL) is defined as the loss of two or more consecutive pregnancies before the 20 weeks of gestation. RPL affects about 1–2% of couples trying to conceive; however, the mechanisms leading to this complication are largely unknown. Our previous studies using comparative proteomics identified 314 differentially expressed proteins (DEPs) in the placental villous. In this study, we identified 5479 proteins from a total of 34 157 peptides in decidua of patients with early RPL (data are available via ProteomeXchange with identifier PXD023849). Further analysis identified 311 DEPs in the decidua tissue; and 159 proteins were highly expressed, whereas 152 proteins were lowly expressed. These 311 proteins were further analyzed by using Ingenuity Pathway Analysis. The results suggested that 50 DEPs played important roles in the embryonic development. Upstream analysis of these DEPs revealed that angiotensinogen was the most important upstream regulator. Furthermore, protein–protein interaction analysis of the embryonic development DEPs from the placental villous and decidua was performed in the STRING database. This study identified several proteins specifically associated with embryonic development in decidua of patients with early RPL. Therefore, these results provide new insights into potential biological mechanisms, which may ultimately inform RPL. Summary sentence Proteomic and functional analysis of decidua in patients with recurrent pregnancy loss. Graphical Abstract

Despite the longstanding evidence on the effect of air pollutants on preterm birth (PTB), few studies have focused on its subtypes, including spontaneous preterm birth (sPTB) and medically indicated preterm birth (miPTB). Most studies evaluated only the short-term or long-term effects of particulate matter (PM) on PTB. Thus, we designed this study, based on a cohort of 179,385 women, to evaluate both short- and long-term effects of PM with diameter2.5 μm and10 μm (PM

Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4–6 months, 7–12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.

Background Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. Methods A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. Results Caregivers tended to underestimate children’s weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children’s physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children’s nutrition intake and physical activity, and preferred online approaches. Conclusions Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

Background Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription. Results Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4 weeks and 7 weeks, respectively. Importantly, except for ~ 1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4 weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300. Conclusions Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.

Previous studies investigated the association between gestational anemia and neonatal outcomes. However, few studies explored whether the effects of gestational anemia could be eliminated by subsequent correction of anemia in the later stages of pregnancy. This study aimed to investigate the relationship between anemia in different trimesters and neonatal outcomes. The study was conducted in Shanghai, China, with a sample of 46,578 pregnant women who delivered between January 1, 2016 and July 1, 2019. A multivariable logistic regression model was adopted to analyse the associations between maternal anemia and neonatal outcomes. The incidence of gestational anemia was 30.2%, including 4.4% in the first trimester, 9.6% in the second trimester, and 16.2% in the third trimester. Only 24.5% (507/2066) of anemia that occurred in the first trimester and 29.6% (1320/4457) that occurred in the second trimester could be corrected in the later stages of pregnancy. Anemia occurring in the first trimester was associated with small for gestational age [odds ratio (OR) 1.46; 95% confidence interval (CI) 1.20–1.78] and with fetal distress (OR 1.23; 95% CI 1.08–1.40). Anemia corrected in the first trimester also was associated with a higher risk of small for gestational age. Gestational anemia is a public health problem in China impacting neonatal health. Anemia in pregnancy could be corrected in only about a quarter of the women. Anemia in the first trimester, whether corrected or not, still led to lower birth weight; therefore, the prevention of anemia prior to pregnancy is important.

Background: The association between isolated maternal hypothyroxinemia (IMH) during pregnancy and preterm birth (PTB), especially for subtypes of PTB, is unclear. This study aimed at determining th...

Context Accurate methods for early gestational diabetes mellitus (GDM) (during the first trimester of pregnancy) prediction in Chinese and other populations are lacking. Objectives This work aimed to establish effective models to predict early GDM. Methods Pregnancy data for 73 variables during the first trimester were extracted from the electronic medical record system. Based on a machine learning (ML)-driven feature selection method, 17 variables were selected for early GDM prediction. To facilitate clinical application, 7 variables were selected from the 17-variable panel. Advanced ML approaches were then employed using the 7-variable data set and the 73-variable data set to build models predicting early GDM for different situations, respectively. Results A total of 16 819 and 14 992 cases were included in the training and testing sets, respectively. Using 73 variables, the deep neural network model achieved high discriminative power, with area under the curve (AUC) values of 0.80. The 7-variable logistic regression (LR) model also achieved effective discriminate power (AUC = 0.77). Low body mass index (BMI) (≤ 17) was related to an increased risk of GDM, compared to a BMI in the range of 17 to 18 (minimum risk interval) (11.8% vs 8.7%, P = .09). Total 3,3,5′-triiodothyronine (T3) and total thyroxin (T4) were superior to free T3 and free T4 in predicting GDM. Lipoprotein(a) was demonstrated a promising predictive value (AUC = 0.66). Conclusions We employed ML models that achieved high accuracy in predicting GDM in early pregnancy. A clinically cost-effective 7-variable LR model was simultaneously developed. The relationship of GDM with thyroxine and BMI was investigated in the Chinese population.

BNC1 is a transcription factor that is crucial for spermatogenesis and male fertility, although the underlying mechanism remains unclear. To study BNC1's specific role in spermatogenesis, we characterized a previously developed mouse model carrying a truncating mutation in Bnc1 (termed Bnc1+/tr for heterozygotes and Bnc1tr/tr for homozygotes) and found that the mutation decreased BNC1 protein levels and resulted in germ cell loss by apoptosis. Given that loss of functional Bnc1 is known to result in decreased expression of the spermatogenesis genes Ybx2 and Papolb, we aimed to explore whether and how BNC1 promotes transcription of Ybx2 and Papolb to mediate its role in spermatogenesis. We confirmed significant reduction in YBX2 and PAPOLB protein levels in testis tissue from Bnc1+/tr and Bnc1tr/tr males compared with wild-type mice (Bnc1+/+). Consistently, knockdown of Bnc1 led to downregulation of Ybx2 and Papolb in CRL-2196 cells in vitro. To investigate if BNC1 directly induces Ybx2 and Papolb gene expression, chromatin immunoprecipitation using mouse testicular tissue and luciferase reporter assays in HEK293 cells were used to identify functional binding of BNC1 to the Ybx2 and Papolb promoters at defined BNC1 binding sites. Taken together, this study reveals a mechanism for BNC1's role in spermatogenesis by directly binding to BNC1 binding elements in the promoter regions of both Ybx2 and Papolb and inducing transcription of these important spermatogenesis genes.

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

Early non-chromosome-related missed abortion (MA) is commonly associated with an altered immunological environment during pregnancy. Human decidual natural killer (dNK) cells, the most abundant lymphocyte population within the first-trimester maternal-fetal interface, are vital maternal regulators of immune tolerance mediating successful embryo implantation and placentation. Previous studies have shown that dNK cells may play a role in MA. However, the gene expression status and specific altered manifestations of dNK cells in patients with early MA remain largely unknown. Here, we show that MA dNK cells have distinct mRNA and lncRNA expression profiles through RNA sequencing, with a total of 276 mRNAs and 67 lncRNAs being differentially expressed compared with controls. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. An lncRNA-mRNA regulatory network characterized by the small-world property was constructed to reveal the regulation of mRNA transcription by differential hub lncRNAs. Functional annotation of differentially expressed mRNAs and lncRNAs was performed to disclose their potential roles in MA pathogenesis. Our data highlight several enriched biological processes (immune response, inflammatory response, cell adhesion, and extracellular matrix [ECM] organization) and signaling pathways (cytokine-cytokine receptor interaction, ECM-receptor interaction, Toll-like receptor signaling pathway, and phosphatidylinositol signaling system) that may influence MA. This study is the first to demonstrate the involvement of altered mRNA and lncRNA expression profiles in the dNK cell pathogenesis of early MA, facilitating a better understanding of the underlying molecular mechanisms and the development of novel MA therapeutic strategies targeting key mRNAs and lncRNAs.

Objective To study the effect of aging on ovarian circadian rhythm. Design Human and animal study. Setting University hospital and research laboratory. Patients/animals Human granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice. Intervention(s) None. Main outcome measure(s) Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice. Result(s) All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P P Conclusion(s) Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.

PurposeHigher serum estradiol levels occur in women undergoing assisted reproductive technology (ART) owing to ovarian stimulation. Here, we investigated the association between maternal serum estradiol levels and the intellectual development of offspring conceived with ART.MethodsA total of 204 singletons born after fresh embryo transfer were recruited for this cohort study. Among them, 102 children were born from mothers with high serum estradiol levels (> 12,000 pmol/L) on the day that human chorionic gonadotropin was administered. Another 102 children, matched by gestational age and age of the children, were recruited as controls from mothers with low serum estradiol (≤ 12,000 pmol/L). The Wechsler Preschool and Primary Scale of Intelligence was used to evaluate the intellectual development of the children.ResultsChildren from mothers with higher serum estradiol levels scored lower in the verbal intelligence quotient (IQ) tests and verbal comprehension than children whose mothers had lower estradiol levels. The main difference between the two groups was in verbal subtests including information, vocabulary, and sorting. Partial correlation analysis revealed that the logarithm of maternal serum estradiol level negatively correlated with verbal IQ, performance IQ, and full scale IQ.ConclusionOur data demonstrate that a high maternal serum estradiol level may negatively associate the verbal ability of children conceived via ART.

Objective To assess whether vaginal secretions and breast milk of women with coronavirus disease 2019 (COVID‐19) contain severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Design Single centre cohort study. Setting Renmin Hospital of Wuhan University, Wuhan, Hubei province, China. Population We studied 13 SARS‐CoV‐2‐infected pregnant women diagnosed between 31 January and 9 March 2020. Methods We collected clinical data, vaginal secretions, stool specimens and breast milk from SARS‐CoV‐2‐infected women during different stages of pregnancy and collected neonatal throat and anal swabs. Main outcomes and measures We assessed viral presence in different biosamples. Results Of the 13 women with COVID‐19, five were in their first trimester, three in their second trimester and five in their third trimester. Of the five women in their third trimester who gave birth, all delivered live newborns. Among these five deliveries, the primary adverse perinatal outcomes included premature delivery (n = 2) and neonatal pneumonia (n = 2). One of nine stool samples was positive; all 13 vaginal secretion samples, and five throat swabs and four anal swabs collected from neonates, were negative for the novel coronavirus. However, one of three samples of breast milk was positive by viral nucleic acid testing. Conclusions In this case series of 13 pregnant women with COVID‐19, we observed negative viral test results in vaginal secretion specimens, suggesting that a vaginal delivery may be a safe delivery option. However, additional research is urgently needed to examine breast milk and the potential risk for viral contamination. Tweetable abstract New evidence for the safety of vaginal delivery and breastfeeding in pregnant women infected with SARS‐CoV‐2, positive viral result in a breast‐milk sample., New evidence for the safety of vaginal delivery and breastfeeding in pregnant women infected with SARS‐CoV‐2, positive viral result in a breast‐milk sample.

Increased granulosa cell (GC) proliferation may contribute to abnormal folliculogenesis in patients with polycystic ovary syndrome (PCOS), which affects approximately 10% reproductive aged women. However, the mechanisms underlying increased GC proliferation in PCOS remain incompletely understood. In this study, we identified miR-3940-5p as a hub miRNA in GC from PCOS using weighted gene co-expression network analysis (WGCNA), and real-time polymerase chain reaction (RT-PCR) analysis confirmed that miR-3940-5p was significantly increased in GC from PCOS. Enrichment analysis of predicted target genes of miR-3940-5p indicated potential roles of miR-3940-5p in follicular development and cell proliferation regulation. Consistently, functional study confirmed that miR-3940-5p overexpression promoted granulosa cell proliferation. Integrated analysis of mRNA expression profiling data and predicted target genes of miR-3940-5p identified potassium voltage-gated channel subfamily A member 5 (KCNA5) as a potential target of miR-3940-5p, and was validated by luciferase reporter assay. Finally, functional analysis suggested that miR-3940-5p promoted GC proliferation in a KCNA5 dependent manner. In conclusion, miR-3940-5p was a hub miRNA upregulated in GC from PCOS, and promoted GC proliferation by targeting KCNA5.

The recommendations for the diagnosis of stage 1 hypertension were recently revised by the American Heart Association primarily based on its impact on cardiovascular disease risks. Whether the newly diagnosed stage 1 hypertension impacts pregnancy complications remain poorly defined. We designed a retrospective cohort study to investigate the associations of stage 1 hypertension detected in early gestation (

To investigate whether there are left–right asymmetries in tubal endometriosis and the factors affecting this predisposition. Women who underwent salpingectomy for gynecological diseases and were diagnosed with tubal endometriosis between January 2002 and July 2019 were included in the study. The frequencies of left and right tubal endometriosis were compared with the expected 50% using a binominal test. The demographic characteristics and presence of ovarian endometrioid cysts, adenomyosis, and hydrosalpinx were also analyzed. During the study period of more than 17 years, 305 women were diagnosed with tubal endometriosis. The distribution of tubal endometriosis in the left or right fallopian tubes was analyzed. Tubal endometriosis was found in the left fallopian tube in 168 (55.08%) women, in the right fallopian tube in 93 (30.49%), and bilaterally in 44 (14.43%). Left unilateral tubal endometriosis was found most frequently (64.37%, 168/261), and its incidence was significantly higher than 50% (P

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

Infertility seriously endangers the reproductive health of women at childbearing age. It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse. Broadly defined, infertility includes two aspects – failure to conceive or have a live birth. This guideline only addressed content relevant to the former. It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, based on relevant guidelines of the World Health Organization, the American Society for Reproductive Medicine, the National Institute for Health and Clinical Excellence, as well as the clinical practice in China. The guideline was reviewed by experts and doctors from medical institutions at all levels, which is applicable to the diagnosis of infertility by physicians in obstetrics, gynecology, and andrology at various medical institutions nationwide.

While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP.The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated.The fitted curves for ICP incidence were similar to the temporal trends of PMExposure to PM

Objective: Poor sleep quality is common during pregnancy. Although a few studies have investigated the associations between maternal sleep quality and fetal birth weight (BW), no evidence has been ...

The prevalence of gestational diabetes mellitus (GDM) is increasing rapidly. In addition to the metabolic disease risks, GDM might increase the risks of cryptorchidism in children. However, its mechanism involved in abnormalities of the male reproductive system is still unclear. The purpose of this study was to study the effects of GDM on the development of mouse fetal Leydig cells (FLCs) and Sertoli cells (SCs). Pregnant mice were treated on gestational days 6.5 and 12.5 with streptozotocin (100 mg/kg) or vehicle (sodium citrate buffer). Leydig cell and SC development and functions were evaluated by investigating serum testosterone levels, cell number and distribution, genes, and protein expression. GDM decreased serum testosterone levels, the anogenital distance, and the level of desert hedgehog in SCs of testes of male offspring. FLC number was also decreased in testes of GDM offspring by delaying the commitment of stem Leydig cells into the Leydig cell lineage. RNA-seq showed that FOXL2, RSPO1/β-catenin signaling was activated and Gsk3β signaling was inhibited in GDM offspring testis. In conclusion, GDM disrupted reproductive tract and testis development in mouse male offspring via altering genes related to development.

A high maternal triglyceride (mTG) level during early pregnancy is linked to adverse pregnancy outcomes, but the use of specific interventions has been met with limited success. A retrospective cohort study was designed to investigate the impact of gestational weight gain (GWG) on the relationship between high levels of mTG and adverse pregnancy outcomes in normal early pregnancy body mass index (BMI) women. The patients included 39,665 women with normal BMI who had a singleton pregnancy and underwent serum lipids screening during early pregnancy. The main outcomes were adverse pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes, cesarean delivery, preterm birth, and large or small size for gestational age (LGA or SGA) at birth. As a result, the high mTG (≥2.05mM) group had increased risks for gestational hypertension ((Adjusted odds ratio (AOR), 1.80, 95% CI, 1.46 to 2.24)), preeclampsia (1.70, 1.38 to 2.11), gestational diabetes (2.50, 2.26 to 2.76), cesarean delivery (1.22, 1.13 to 1.32), preterm birth (1.42, 1.21 to 1.66), and LGA (1.49, 1.33 to 1.68) compared to the low mTG group, after adjustment for potential confounding factors. Additionally, the risks of any adverse outcome were higher in each GWG subgroup among women with high mTG than those in the low mTG group. High mTG augmented risks of gestational hypertension, preeclampsia, preterm birth, and LGA among women with 50th or greater percentile of GWG. Interestingly, among women who gained less than the 50th percentile of GWG subgroups, there was no relationship between high mTG level and risks for those pregnancy outcomes when compared to low mTG women. Therefore, weight control and staying below 50th centile of the suggested GWG according to gestational age can diminish the increased risks of adverse pregnancy outcomes caused by high mTG during early pregnancy.

Background Nicolaides–Baraitser syndrome (NCBRS) is a severe neurodevelopmental disorder with multiple abnormalities. To date, all pathogenic variants in SMARCA2 causing NCBRS are de novo and most are missense variants located in the ATPase domain of SMARCA2 protein. Methods In this study, a familial trio whole‐exome sequencing was performed on the proband presenting with intellectual disability, early‐onset epilepsy, and autistic features. A novel missense variant c.553C>G (p.Gln185Glu) in SMARCA2 was identified, which is located in the QLQ domain. The same variant was subsequently also found in the mother's ongoing pregnancy. Samples from accessible tissues such as saliva and sperm other than blood were collected from the parents, and the detection of the target variant was performed by amplicon‐based deep sequencing. Results Low‐level mosaicism of the target variant c.553C>G (p.Gln185Glu) was detected in the father's sperm with allele fraction of 2.8% by amplicon‐based deep sequencing, which was not detected in either parents’ blood or saliva specimens. Heterozygosity of this variant was confirmed in the proband. Conclusion This is the first report of paternal germline mosaicism for a SMARCA2 disease‐causing variant. In addition, the missense variant c.553C>G (p.Gln185Glu) in the QLQ domain causes mainly neurological and developmental phenotypes with unremarkable characteristic facial features and limb abnormalities. Our findings expand the phenotypic spectrum and mode of genetic transmission associated with the SMARCA2 variants., A novel SMARCA2 missense variant in the proband was found due to low‐level paternal germline mosaicism as the first disease‐causing variant in the QLQ domain associated with solely neurological and developmental phenotypes of NCBRS, which provides new insights into the structure–function relationship of this subunit in the SWI/SNF complexes.

Background The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. Methods/design A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. Discussion To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. Trial registration number ChiCTR, ChiCTR1900026963. Registered 27 October 2019.

Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes (DEGs) were enriched in neurodevelopment and synaptic plasticity. The reduced representation bisulfite sequencing (RRBS) of sperm in F1 adult males showed that the intrauterine hyperglycemia exposure caused altered methylated modification of F1 sperm, which is a potential epigenetic mechanism for the intergenerational neurocognitive effects of GDM.

Background: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. Method: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). Results: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03–1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04–1.79). Conclusion: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy.

We conducted a retrospective cohort study of 9,552 women experiencing their second delivery between 2014 and 2016 at the International Peace Maternity and Child Health Hospital to investigate the association between the interpregnancy interval (IPI) and adverse perinatal outcomes. With the 12-23-mon IPI as the reference category, logistic regression analyzes were used to examine associations between different IPIs (

Vitamin D deficiency during pregnancy is a worldwide epidemic. This study aimed to identify whether vitamin D deficiency in early pregnancy is associated with placental inflammation in high-risk pregnancy.This study comprised 23,396 women who provided serum samples in the first trimester for vitamin D analysis from January 2015 to December 2016. Among them, 2648 women with high-risk pregnancy underwent placental pathologic examination. Women were divided into placental inflammation positive (PIP) and placental inflammation negative (PIN) groups based on placental pathology. Multivariate logistic regression was used to evaluate the relationship between vitamin D levels and placental inflammation.We found that severe vitamin D deficiency in early pregnancy was associated with placental inflammation. Maternal vitamin D levels were significantly lower in the PIP group than those in the PIN group (P = 0.025). Compared with the highest quartile of vitamin D levels, risk for placental inflammation was significantly higher in women with extremely low vitamin D levels (5th percentile; P = 0.012). The effect estimate was slightly decreased but still significant (P = 0.027) after adjusting for maternal age, gestational age at birth, birth weight, infant sex, and sample collection season. In addition, compared with the PIN group, the incidences of adverse neonatal outcomes, including sepsis (0.5% vs 2.4%) and fetal intrauterine infection (5.7% vs 15.6%), were significantly higher in the PIP group than that in the PIN group (P 0.001).Severe vitamin D deficiency in the first trimester is a risk factor for placental inflammation in high-risk pregnancy.

The pathophysiology of preeclampsia (PE) remains unclear. PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern. We collected placental and umbilical artery samples from nor-motensive and PE pregnancies. Mineralocorticoid receptor (MR) and its alternative splicing variant (ASV) expression and their biological effects on PE were examined. An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples (umbilical artery, ~57.58%; placenta, ~36.84%). The MR ASV expression was positively associated with blood pressure in both groups. The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways. The MR ASV can also impair the proliferation, migration, and tube formation ability of endothelial cells. These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology, especially in endothelial dysfunction, and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases.